This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Simian immunodeficiency virus (SIV) becomes more virulent upon in vivo evolution. Also, tissue specific variants have been identified that may impact infection and disease. The mechanisms by which SIV acquires increased potential to replicate, and thereby drive disease progression, are not well understood. Identifying the molecular determinants of virulence will provide a basis for uncovering the host-virus interactions important for efficient virus replication. The goal of the study is to identify the molecular determinants of a lymph node (LN)-derived SIV variant that enable it to replicate in resting peripheral blood mononuclear cells, and to define the host cell interactions important for supporting virus replication.